The iron (III) chelate of desferrioxamine B is a known magnetic resonance imaging contrast agent that gives both renal and hepatobiliary enhancement. It is one of the soluble paramagnetic compounds used for this purpose. Other soluble paramagnetic compounds, such as Gd-DTPA, suffer from various disadvantages, such as, rapid diffusion from the vascular system into the extracellular space, lack of specificity for liver and essentially no concentration in the bile. Manganese dichloride concentrates in the liver after IV injection, is transported to the bile and excreted in the feces, however, it is toxic and is not practically useful in a clinical situation. Iron (III) complexes Fe-EHPF and Fe-HBED are useful contrast agents in the liver and are secreted into the bile. However, their appearance in the bile does not take place until approximately 20 minutes post injection and furthermore, enhancement of the lumen of the small intestine is seldom observed using these agents.
The magnetic resonance imaging of the gastrointestinal tract is limited by inherently low image contrast, motion and variable anatomic appearance. Agents for this purpose are normally administered orally and reside within lumen of the GI tract to provide either positive (increased signal strength) or negative (decreased signal strength) contrast. In the usual situation, positive contrast is provided by ingestion of paramagnetic agents such as Gd-DTPA or iron citrate while negative contrast is provided by displacement of the luminal proton-containing contents by gas (such as carbon dioxide from gas tablets) or perfluorocarbons. Negative contrast can also be obtained by ingestion of ferromagnetic or superparamagnetic particles, such as ferrite.
There is thus a need in the art for MRI contrast agents which are useful both for hepatobiliary studies and for gastrointestinal studies, particularly when introduced by intravenous administration, rather than by oral administration.
It is thus an object of the present invention to provide improved desferrioxamine B contrast agents for magnetic resonance imaging.
It is yet another object of the present invention to provide magnetic resonance imaging contrast agents having high stability, low toxicity, physiological tolerability and which provide for positive imaging of the small intestine rapidly after intravenous administration.
It is a further object of the present invention to provide desferrioxamine B contrast agents which are organ selective.